Bevacizumab With or Without TRC105 in Treating Patients With Metastatic Kidney Cancer

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This randomized phase II trial studies how well bevacizumab with or without anti-endoglin monoclonal antibody TRC105 (TRC105) works in treating patients with kidney cancer that has spread to other parts of the body (metastatic). Monoclonal antibodies, such as bevacizumab and anti-endoglin monoclonal antibody TRC105, may block tumor growth in different ways by targeting certain cells.

II. To compare the soluble CD105 levels at baseline and after treatment between the group receiving bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin monoclonal antibody TRC105.

III. To compare TGFBR2 levels at baseline and after treatment between the group receiving bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin monoclonal antibody TRC105.

IV. To evaluate whether circulating tumor cells (CTCs) can be detected in this patient population using parylene membrane filter technology, and whether changes in CTC counts and CD105 expression on CTCs during therapy correspond to imaging and clinical response.

Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must have histologically or cytologically confirmed renal cancer; all histologic subtypes will be eligible

Patients must have metastatic disease which is measurable, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) to >= 20 mm in the long axis by chest x-ray, >= 10 mm in the long axis by spiral computed tomography (CT), magnetic resonance imaging (MRI), calipers, or clinical exam, or >= 15 mm in the short axis for lymph nodes

Patients must have received at least 1 prior systemic therapy for renal cancer but no more than 4 prior therapies; they must have documented intolerance to or progression despite at least 1 systemic therapy; therapy administered in the adjuvant setting counts toward the prior systemic therapy total; if adjuvant therapy is the patient's only prior therapy the disease must have recurred during treatment or within 3 months of discontinuation

At least 2 weeks must have elapsed from the last dose of the prior systemic therapy for biologics and 4 weeks for chemotherapy (6 weeks for nitrosoureas or mitomycin C); also note that at least 3 weeks should have elapsed since prior TKI administration

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of TRC105 or bevacizumab administration

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Patients who have had systemic biologic therapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events related to their prior therapy

Patients who have previously been treated with bevacizumab

Patients who have previously been treated with TRC105

Patients who are receiving any other investigational agents

Known central nervous system (CNS) disease except for treated brain metastasis; treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (MRI or CT) (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded

History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC105 or bevacizumab

Patients on full-dose anticoagulation will be excluded; antiplatelet therapy will not be exclusionary

Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother wishes to participate in the study

Patients with a history of bleeding diathesis or inherited coagulopathy are excluded; in addition, those with a history of deep vein thrombosis (DVT) or pulmonary embolus within 1 year and still requiring active anticoagulation will be excluded; those with a more remote history of DVT or pulmonary embolus may be eligible but the risk of recurrent thrombosis should be considered

Patients with history of hereditary hemorrhagic telangiectasis (HHT-1 and HHT-2)

Serious or non-healing wound, ulcer, or bone fracture OR history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1

Invasive procedures defined as follows:

Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1 therapy

Anticipation of need for major surgical procedures during the course of the study